Genetic Variation Doubles Risk of Liver Cancer

WEDNESDAY, Jan. 2 -- A single change in the epidermal growth factor (EFG) gene may double the risk of developing liver tumors, especially among people with cirrhosis, new research suggests.

Hepatocellular carcinoma is a liver tumor that is the third leading cause of cancer death and may result from this genetic variation, said the researchers. It is also the sixth most common solid tumor worldwide and often develops in people who have cirrhosis.

Cirrhosis is a liver disease that can result from long-term alcohol abuse or infection with the hepatitis C or B viruses. According to the U.S. National Cancer Institute, about five percent of people with cirrhosis will develop liver cancer.

The research, published in the Jan. 2 edition of the Journal of the American Medical Association, suggested that people who have one or two guanine nucleotides at the EFG gene site, instead of two adenine nucleotides, are at significantly greater risk of cancer.

"If these results are confirmed, this EGF variation could be used to determine which cirrhotic patients should be screened more intensively for tumor development," lead author Dr. Kenneth Tanabe, chief of surgical oncology at the Massachusetts General Hospital Cancer Center, said in a prepared statement. "In addition, the molecular pathway controlled by EGF and its receptor, EGFR, which is known to be important in several types of cancer, appears to be an excellent target for chemoprevention studies. This is a deadly cancer, and so progress in prevention and early detection is critically important."

The EFG gene normally works to increase tissue growth through the production of EFG protein. Animal studies previously demonstrated a link between high levels of EFG and tumor development. Blocking the protein's receptor has been shown to prevent tumor growth. This is the first study to assess the relationship in humans, according to the researchers.

When the EFG gene contains one or two guanine nucleotides (guanine instead of the more common adenine), EFG is present in a greater quantity in the blood, raising the carrier's risk of cancer, the study found.

Knowing this, the research team analyzed tissue samples from 207 Massachusetts General Hospital patients with cirrhosis, the majority of whom were infected with hepatitis C. Of that group, 59 had a hepatocellular carcinoma. The researchers found that patients with at least one copy of the guanine nucleotide were two times more likely than patients with only adenine nucleotides to develop liver tumors. Patients with two guanine nucleotides were four times more likely to develop liver tumors.

The researchers also found that EFG levels were highest in those people with two guanine nucleotides.

The team then analyzed data from patients at the Paul Brousse Hospital in Paris, most of whom suffered from alcoholic cirrhosis. These patients were three times more likely to have a liver tumor if they had two guanine nucleotides than if they had two adenine nucleotides.

The researchers noted that age and gender had no effect on the genetic risk of developing the tumor. The majority of the subjects were Caucasian, but the researchers found an increased risk of the genetic variation among Asian patients. More than half of hepatocellular cancer cases worldwide occur in China.

Tanabe and his colleagues called for a study of patients with cirrhosis before the development of liver cancer to better understand other variables, such as diet and medications, that could affect EFG levels.